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Background: Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A(225)) acetylates HIF-1alpha, triggering its degradation, and thus may play a role in decreased expression of VEGFA.Methods: We generated Apc(Min/+)/mARD1A(225) transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A(225) were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A(225) acetylation of Lys532 in HIF-1alpha, we injected B16F10-mARD1A(225) cell lines stably expressing mutant HIF-1alpha/K532R into mice and measured metastasis. All statistical tests were two-sided, and P values less than .05 were considered statistically significant.Results: Apc(Min/+)/mARD1A(225) transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than Apc(Min/+) mice (n = 21) (number of intestinal polyps per mouse: Apc(Min/+) mice vs Apc(Min/+)/mARD1A(225) transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; P < .001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A(225)-overexpressing cells than in mice injected with control cells (P < .01). Moreover, overexpression of mARD1A(225) decreased VEGFA expression and microvessel density in tumor xenografts (P < .04) and Apc(Min/+) intestinal polyps (P = .001). Mutation of lysine 532 of HIF-1alpha in B16F10-mARD1A(225) cells prevented HIF-1alpha degradation and inhibited the antimetastatic effect of mARD1A(225) (P < .001).Conclusion: mARD1A(225) may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most lethal types of human brain cancer and is characterized by rapid growth, an aggressive nature and a poor prognosis. GBM is highly heterogeneous, and often involves several genetic mutations and abnormalities. Genetic disorders or low expression of phosphatase and tensin homolog (PTEN) are associated with GBM occurrence, progression and poor prognosis of patients with GBM. However, effective delivery of PTEN for expression in GBM cells within the brain remains challenging. The aim of the present study was to develop a therapeutic strategy to restore PTEN expression in GBM cells by utilizing a recombinant Newcastle disease virus (rNDV) vector expressing the human PTEN gene (rNDV-PTEN). Methods included infection of U87-MG cells with rNDV-PTEN, followed by assessments of PTEN expression, and cell proliferation, migration and apoptosis. Additionally, an orthotopic GBM mouse model was used to evaluate the in vivo efficacy of rNDV-PTEN. Infection with recombinant rNDV-PTEN treatment increased PTEN protein expression in the cytoplasm of the U87-MG cells, reduced cell proliferation and migration, and induced apoptosis by inhibiting the AKT/mTOR signaling pathway. In the orthotopic GBM mouse model, rNDV-PTEN significantly reduced tumor size and improved survival rates. Magnetic resonance imaging and in vivo imaging analyses confirmed the targeted delivery and efficacy of rNDV-PTEN. These findings highlight the usefulness of rNDV-PTEN as a promising therapeutic agent for GBM, representing a potential advancement in treatment, especially for patients with PTEN deficiency., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kim et al.)

Background: With decades of containment efforts, the prevalence of C. sinensis infection in Korea has shown a declining trend. However, well-tailored intervention assessments remain challenging, particularly when considering the potential impacts of cohort variations in raw freshwater fish consumption behavior, a major transmission route to humans, on this observed decline., Methodology: We applied an age-period-cohort modeling approach to nationally representative C. sinensis infection prevalence data from 1981-2012 in Korea to assess age, period, and cohort effects on its secular trend and to project the age-stratified prevalence up to 2023., Principal Findings: Our analysis suggests that both cohort and period effects have substantially contributed to the declining prevalence of C. sinensis infection in Korea. Age-stratified projections up to 2023 suggest a decline in prevalence across all age groups, while those aged over 40 are anticipated to maintain prevalences above the elimination threshold of 1%., Conclusions: Our study highlights the importance of incorporating cohort effects into intervention assessments aimed at controlling C. sinensis infection. The effectiveness of interventions remains evident in Korea despite adjusting for the cohort effect. This approach, applicable to other endemic countries, would provide valuable insights for intervention assessments and inform future public health planning to eliminate C. sinensis infection., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: J-hJ and M-RL are affiliated with the Division of Vectors and Parasitic Diseases, Korea Disease Control and Prevention Agency. The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the Korea Disease Control and Prevention Agency. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the Korean government., (Copyright: © 2024 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Using their light wing and through the use of a leading-edge vortex (LEV), autorotating samaras can generate high lift while descending at extremely low speeds. But the flight performance of the samara, with respect to the wide design envelope, is still not well understood. Therefore, this paper aims to experimentally assess how the flight performance of three natural samara wings varies with differing wind speeds and flight conditions. The tests were conducted within a vertical wind tunnel and a novel rig was devised to effectively measure the vertical thrust and rotational rate of the autorotating samara at near frictionless conditions. Furthermore, a bespoke hub was implemented to control the coning and pitch angles of the samara wing. The tests generated a novel and comprehensive set of experimental data of autorotating samaras with changing wind speed, coning and pitch angles. The results also revealed that coning angles between 5 and 15 degrees can increase the vertical thrust produced by the samara by up to a maximum of 9.6 % . Additionally, it was found that samaras operate at extremely low pitch angles between -0.7 and -2.6 degrees to maximise their thrust, even though the conditions are close to the autorotational stability boundary., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

In this study, a novel synthesis of ultrathin, highly uniform colloidal bismuth sulfohalide (BiSX where X = Cl, Br, I) nanowires (NWs) and NW bundles (NBs) for room-temperature and solution-processed flexible photodetectors are presented. High-aspect-ratio bismuth sulfobromide (BiSBr) NWs are synthesized via a heat-up method using bismuth bromide and elemental S as precursors and 1-dodecanethiol as a solvent. Bundling of the BiSBr NWs occurs upon the addition of 1-octadecene as a co-solvent. The morphologies of the BiSBr NBs are easily tailored from sheaf-like structures to spherulite nanostructures by changing the solvent ratio. The optical bandgaps are modulated from 1.91 (BiSCl) and 1.88 eV (BiSBr) to 1.53 eV (BiSI) by changing the halide compositions. The optical bandgap of the ultrathin BiSBr NWs and NBs exhibits blueshift, whose origin is investigated through density functional theory-based first-principles calculations. Visible-light photodetectors are fabricated using BiSBr NWs and NBs via solution-based deposition followed by solid-state ligand exchanges. High photo-responsivities and external quantum efficiencies (EQE) are obtained for BiSBr NW and NB films even under strain, which offer a unique opportunity for the application of the novel BiSX NWs and NBs in flexible and environmentally friendly optoelectronic devices., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

A woman in South Korea who underwent a colonoscopy for occasional gastrointestinal discomfort had 4 adult flukes of Echinostoma cinetorchis showing 37 collar spines around the oral sucker recovered from the terminal ileum through the ascending colon. Partial gene sequencing showed high identity with E. cinetorchis.

Perovskite nanocrystals (NCs) have emerged as a promising building block for the fabrication of optic-/optoelectronic-/electronic devices owing to their superior characteristics, such as high absorption coefficient, rapid ion mobilities, and tunable energy levels. However, their low structural stability and poor surface passivation have restricted their application to next-generation devices. Herein, a drug delivery system (DDS)-inspired post-treatment strategy is reported for improving their structural stability by doping of Ag into CsPbBr 3 (CPB) perovskite NCs; delivery to damaged sites can promote their structural recovery slowly and uniformly, averting the permanent loss of their intrinsic characteristics. Ag NCs are designed through surface-chemistry tuning and structural engineering to enable their circulation in CPB NC dispersions, followed by their delivery to the CPB NC surface, defect-site recovery, and defect prevention. The perovskite-structure healing process through the DDS-type process (with Ag NCs as the drug) is analyzed by a combination of theoretical calculations (with density functional theory) and experimental analyses. The proposed DDS-inspired healing strategy significantly enhances the optical properties and stability of perovskite NCs, enabling the fabrication of white light-emitting diodes., (© 2023 Wiley‐VCH GmbH.)

The demand for self-powered photodetectors (PDs) capable of NIR detection without external power is growing with the advancement of NIR technologies such as LIDAR and object recognition. Lead sulfide quantum dot-based photodetectors (PbS QPDs) excel in NIR detection; however, their self-powered operation is hindered by carrier traps induced by surface defects and unfavorable band alignment in the zinc oxide nanoparticle (ZnO NP) electron-transport layer (ETL). In this study, an effective azide-ion (N 3 - ) treatment is introduced on a ZnO NP ETL to reduce the number of traps and improve the band alignment in a PbS QPD. The ZnO NP ETL treated with azide ions exhibited notable improvements in carrier lifetime and mobility as well as an enhanced internal electric field within the thin-film heterojunction of the ZnO NPs and PbS QDs. The azide-ion-treated PbS QPD demonstrated a increase in short-circuit current density upon NIR illumination, marking a responsivity of 0.45 A W -1 , specific detectivity of 4 × 10 11 Jones at 950 nm, response time of 8.2 µs, and linear dynamic range of 112 dB., (© 2023 Wiley‐VCH GmbH.)

Various pathogens can cause upper respiratory tract infections, presenting challenges in accurate diagnosis due to similar symptomatology. Therefore, rapid and precise diagnostic tests are crucial for effective treatment planning. Traditional culture-based methods for diagnosis are limited by their reliance on skilled personnel and lengthy processing times. In contrast, multiplex polymerase chain reaction (PCR) techniques offer enhanced accuracy and speed in identifying respiratory pathogens. In this study, we aimed to assess the efficacy of the FilmArray™ Respiratory Panel (RP), a multiplex PCR test capable of simultaneously screening 20 pathogens. This retrospective analysis was conducted at Dankook University Hospital, South Korea, between January 2018 and December 2022. Samples from patients with upper respiratory tract infections were analyzed. Results revealed adenovirus as the most prevalent pathogen (18.9%), followed by influenza virus A (16.5%), among others. Notably, a 22.5% co-infection rate was observed. The FilmArray™ RP method successfully identified 20 pathogens within 2 h, facilitating prompt treatment decisions and mitigating unnecessary antibiotic prescriptions. This study underscores the utility of multiplex PCR in respiratory pathogen identification, offering valuable insights for epidemiological surveillance and diagnosis.

A high prevalence of Echinostoma mekongi infection (13.9%; 260/1,876) was found among schoolchildren and adults in Kandal Province, Cambodia, by fecal examination, worm expulsion, and molecular analysis of cox1 and nd1 genes. The source of infection was consumption of Pila sp. snails, a finding confirmed morphologically and molecularly.

In this study, we present ultrasensitive infrared photodiodes based on PbS colloidal quantum dots (CQDs) using a double photomultiplication strategy that utilizes the accumulation of both electron and hole carriers. While electron accumulation was induced by ZnO trap states that were created by treatment in a humid atmosphere, hole accumulation was achieved using a long-chain ligand that increased the barrier to hole collection. Interestingly, we obtained the highest responsivity in photo-multiplicative devices with the long ligands, which contradicts the conventional belief that shorter ligands are more effective for optoelectronic devices. Using these two charge accumulation effects, we achieved an ultrasensitive detector with a responsivity above 7.84 × 10 2 A W -1 and an external quantum efficiency above 10 5 % in the infrared region. We believe that the photomultiplication effect has great potential for surveillance systems, bioimaging, remote sensing, and quantum communication.

In this study, we conducted a survey targeting 191 physical therapists (PTs) and 159 occupational therapists (OTs) in South Korea to explore attitudes toward virtual rehabilitation. Utilizing the Korean version of the ADOPT VR by Glegg et al., OT exhibited significantly more experience with virtual reality (VR) and active video games (AVG) than PT. Therapists with VR/AVG experience scored significantly higher in most categories, and the scores in each category were significantly correlated with the Behavioral Intention category, reflecting the willingness to use VR/AVG. The biggest barriers identified were insufficient funds and setup assistance for the equipment. Differences in responses between the groups with and without VR/AVG experience were most prominent in terms of lack of interest and funding. Therapists' attitudes, perceptions, and intentions toward VR/AVG are crucial factors in the establishment and implementation of VR/AVG; thus, the results of this study provide valuable evidence for future policies related to VR/AVG in rehabilitation medicine., Competing Interests: Conflict of Interest: The authors have no potential conflicts of interest to disclose., (Copyright © 2024. Korean Society for Neurorehabilitation.)

Interleukin-2 (IL-2) induces contrasting immune responses depending on its binding receptor subunit; thus, selective receptor binding is considered a key challenge in cancer therapeutic strategies. In this study, we aimed to investigate the inhibition of IL-2 action and antitumor activity of celastrol (CEL), a compound identified in a screen for IL-2/CD25 binding inhibitors, and to elucidate the underlying role of CEL in immune cells. We found that CEL selectively impairs the binding of IL-2 and CD25 and directly binds to IL-2 but not to CD25. CEL significantly suppressed the proliferation and signaling of IL-2-dependent murine T cells and interfered with IL-2-responsive STAT5 phosphorylation in IL-2 reporter cells and human PBMCs. After confirming the impact of CEL on IL-2, we evaluated its antitumor activity in C57BL/6 mice bearing B16F10 tumors and found that CEL significantly inhibited tumor growth by increasing CD8 + T cells. We also found that CEL did not inhibit tumor growth in T cell-deficient BALB/c nude mice, suggesting that its activity was mediated by the T-cell response. Moreover, combination therapy with low-dose CEL and a TNFR2 antagonist synergistically improved the therapeutic efficacy of the individual monotherapies by increasing the ratio of intratumoral CD8/Treg cells and suppressing Foxp3 expression. These findings suggest that CEL, which inhibits CD25 binding by targeting IL-2, exerts antitumor activity by mediating the T-cell response and could be a promising candidate for combination therapy in cancer immunotherapy against melanoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Oncolytic viruses are being studied and developed as novel cancer treatments. Using directed evolution technology, structural modification of the viral surface protein increases the specificity of the oncolytic virus for a particular cancer cell. Newcastle disease virus (NDV) does not show specificity for certain types of cancer cells during infection; therefore, it has low cancer cell specificity. Hemagglutinin is an NDV receptor-binding protein on the cell surface that determines host cell tropism. NDV selectivity for specific cancer cells can be increased by artificial amino acid changes in hemagglutinin neuraminidase HN proteins via directed evolution, leading to improved therapeutic effects., Methods: Sialic acid-binding sites (H domains) of the HN protein mutant library were generated using error-prone PCR. Variants of the H domain protein were screened by enzyme-linked immunosorbent assay using HCT 116 cancer cell surface molecules. The mutant S519G H domain protein showed the highest affinity for the surface protein of HCT 116 cells compared to that of different types of cancer cells. This showed that the S519G mutant H domain protein gene replaced the same part of the original HN protein gene, and S519G mutant recombinant NDV (rNDV) was constructed and recovered. S519G rNDV cancer cell killing effects were tested using the MTT assay with various cancer cell types, and the tumor suppression effect of the S519G mutant rNDV was tested in a xenograft mouse model implanted with cancer cells, including HCT 116 cells., Results: S519G rNDV showed increased specificity and enhanced killing ability of HCT 116 cells among various cancer cells and a stronger suppressive effect on tumor growth than the original recombinant NDV. Directed evolution using an artificial amino acid change in the NDV HN (S519G mutant) protein increased its specificity and oncolytic effect in colorectal cancer without changing its virulence., Conclusion: These results provide a new methodology for the use of directed evolution technology for more effective oncolytic virus development., (© 2024. The Author(s).)

Digenetic trematodes infecting humans are more than 109 species that belong to 49 genera all over the world. According to their habitat in the definitive hosts, they are classified as 6 blood flukes (Schistosoma japonicum. S. mekongi, S. malayensis, S. mansoni, S. intercalatum, and S. haematobium), 15 liver flukes (Fasciola hepatica, F. gigantica, Clonorchis sinensis, Opisthorchis viverrini, O. felineus, Dicrocoelium dendriticum, D. hospes, Metorchis bilis, M. conjunctus, M. orientalis, Amphimerus sp., A. noverca, A. pseudofelineus, Pseudamphistomum truncatum, and P. aethiopicum), nine lung flukes (Paragonimus westermani, P. heterotremus, P. skrjabini, P. skrjabini miyazakii, P. kellicotti, P. mexicanus, P. africanus, P. uterobilateralis, and P. gondwanensis), 30 heterophyid intestinal flukes (Metagonimus yokogawai, M. takahashii, M. miyatai, M. suifunensis, M. katsuradai, M. pusillus, M. minutus, Heterophyes heterophyes, H. nocens, H. dispar, Haplorchis taichui, H. pumilio, H. yokogawai, H. vanissinus, Centrocestus formosanus, C. armatus, C. cuspidatus, C. kurokawai, Procerovum calderoni, P. varium, Pygidiopsis genata, P. summa, Stictodora fuscata, S. lari, Stellantchasmus falcatus, Heterophyopsis continua, Acanthotrema felis, Apophallus donicus, Ascocotyle longa, and Cryptocotyle lingua), 24 echinostome intestinal flukes (Echinostoma revolutum, E. cinetorchis, E. mekongi, E. paraensei, E. ilocanum, E. lindoense, E. macrorchis, E. angustitestis, E. aegyptica, Isthmiophora hortensis, I. melis, Echinochasmus japonicus, E. perfoliatus, E. lilliputanus, E. caninus, E. jiufoensis, E. fujianensis, Artyfechinostomum malayanum, A. sufrartyfex, A. oraoni, Acanthoparyphium tyosenense, Echinoparymphium recurvatum, Himasthla muehlensi, and Hypoderaeum conoideum), 23 miscellaneous intestinal flukes (Brachylaima cribbi, Caprimolgorchis molenkampi, Phaneropsolus bonnei, P. spinicirrus, Cotylurus japonicus, Fasciolopsis buski, Gastrodiscoides hominis, Fischoederius elongatus, Watsonius watsoni, Gymnophalloides seoi, Gynaecotyla squatarolae, Microphallus brevicaeca, Isoparorchis hypselobagri, Nanophyetus salmincola, N. schikobalowi, Neodiplostomum seoulense, Fibricola cratera, Plagiorchis muris, P. vespertilionis, P. harinasutai, P. javensis, P. philippinensis, and Prohemistomum vivax), one throat fluke (Clinostomum complanatum), and one pancreatic fluke (Eurytrema pancreaticum). The mode of transmission to humans includes contact with cercariae contaminated in water (schistosomes) or ingestion of raw or improperly cooked food, including fish (liver flukes, heterophyid flukes, echinostomes, and throat flukes), snails (echinostomes, brachylaimids, and gymnophallid flukes), amphibia, reptiles (neodiplostomes), aquatic vegetables (fasciolids and amphistomes), and insect larvae or adults (lecithodendriids, plagiorchiids, and pancreatic flukes). Praziquantel has been proven to be highly effective against almost all kinds of trematode infections except Fasciola spp. Epidemiological surveys and detection of human infections are required for a better understanding of the prevalence, intensity of infection, and geographical distribution of each trematode species., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Quantum dot photodiodes (QPDs) have garnered significant attention because of their unparalleled near-infrared (NIR) detection capabilities, primarily attributable to their size-dependent bandgap tunability. Nevertheless, the broadband absorption spectrum of QPD engenders substantial noise floor within superfluous visible light regions, notably hindering their use in several emerging applications necessitating the detection of faint micro-light signals. To overcome these hurdles, a self-screenable NIR QPD featuring an internal optical filter with a thick polymeric interlayer to reduce electronic noise is demonstrated. This effectively screens out undesirable visible light regions while reducing the ionized defect owing to decreased density of state, yielding an extremely low dark current (≈10 10 A cm -2 at V = -1 V). Consequently, the electronic noise spectral density is attained at levels below ≈10 -27 -10 -28 A 2 Hz -1 , and responsivity (R) dropped to 92% within the visible light spectrum., (© 2023 Wiley-VCH GmbH.)

Pancreatic cancer remains one of the deadliest cancers with extremely high mortality rate, and the number of cases is expected to steadily increase with time. Pancreatic cancer is refractory to conventional cancer treatment options, like chemotherapy and radiotherapy, and commercialized immunotherapeutics, owing to its immunosuppressive and desmoplastic phenotype. Due to these reasons, development of an innovative treatment option that can overcome these challenges posed by the pancreatic tumor microenvironment (TME) is in an urgent need. The present review aims to summarize the evolution of oncolytic adenovirus (oAd) engineering and usage as therapeutics (either monotherapy or combination therapy) over the last decade to overcome these hurdles to instigate a potent antitumor effect against desmoplastic and immunosuppressive pancreatic cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JinWoo Hong, Bo-Kyeong Jung, and Hyo Min Ahn are employees of GeneMedicine Co., Ltd. Chae-Ok Yun is the CEO of GeneMedicine Co., Ltd. The funders had no role in the writing of the manuscript., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Colloidal quantum dots (CQDs) are finding increasing applications in optoelectronic devices, such as photodetectors and solar cells, because of their high material quality, unique and attractive properties, and process flexibility without the constraints of lattice match and thermal budget. However, there is no adequate device model for colloidal quantum dot heterojunctions, and the popular Shockley-Quiesser diode model does not capture the underlying physics of CQD junctions. Here, we develop a compact, easy-to-use model for CQD devices rooted in physics. We show how quantum dot properties, QD ligand binding, and the heterointerface between quantum dots and the electron transport layer (ETL) affect device behaviors. We also show that the model can be simplified to a Shockley-like equation with analytical approximate expressions for reverse saturation current, ideality factor, and quantum efficiency. Our model agrees well with the experiment and can be used to describe and optimize CQD device performance.

T. gondii is a highly prevalent parasite worldwide, with cats serving as its final host. However, few studies have investigated the impact of T. gondii infection on cat gut microbiota. Therefore, this study examined the influence of T. gondii infection on the gut microbiota of stray cats and identified potential pathogens in their feces. This study examined T. gondii infection through blood of stray cats and the influence of microbiota in their feces using 16S rRNA gene amplicon sequencing. The results revealed significant differences in gut microbiota composition and diversity between the T. gondii seropositive and seronegative groups. Seropositive samples displayed a lower number of operational taxonomic units and reduced Shannon index than the seronegative samples. The seropositive and seronegative groups exhibited enrichment of taxa, including Escherichia and Enterobacteriaceae and Collinsella, Bifidobacterium, and Roseburia, respectively. Furthermore, potential pathogen species, including Campylobacter, Escherichia, and Streptococcus, were identified in the fecal samples. These findings suggest that T. gondii infection significantly impacts gut microbiota composition and diversity in stray cats. Additionally, an increased potential pathogen load, represented by Escherichia spp., was observed. These results underscore the importance of monitoring the prevalence of zoonotic pathogens in stray cats, as they can serve as reservoirs for zoonotic diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glial cell activation precedes neuronal cell death during brain aging and the progression of neurodegenerative diseases. Under neuroinflammatory stress conditions, lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin or 24p3, is produced and secreted by activated microglia and reactive astrocytes. Lcn2 expression levels are known to be increased in various cells, including reactive astrocytes, through the activation of the NF-κB signaling pathway. In the central nervous system, as LCN2 exerts neurotoxicity when secreted from reactive astrocytes, many researchers have attempted to identify various strategies to inhibit LCN2 production, secretion, and function to minimize neuroinflammation and neuronal cell death. These strategies include regulation at the transcriptional, posttranscriptional, and posttranslational levels, as well as blocking its functions using neutralizing antibodies or antagonists of its receptor. The suppression of NF-κB signaling is a strategy to inhibit LCN2 production, but it may also affect other cellular activities, raising questions about its effectiveness and feasibility. Recently, LCN2 was found to be a target of the autophagy‒lysosome pathway. Therefore, autophagy activation may be a promising therapeutic strategy to reduce the levels of secreted LCN2 and overcome neurodegenerative diseases. In this review, we focused on research progress on astrocyte-derived LCN2 in the central nervous system., (© 2023. The Author(s).)

Background: TRAIL is an anticancer drug that induces cancer cell apoptosis by interacting with death receptors (DRs). However, owing to low cell-surface expression of DRs, certain colorectal cancer (CRC) cells resist TRAIL-induced apoptosis. Newcastle disease virus (NDV) infection can elevate DR protein expression in cancer cells, potentially influencing their TRAIL sensitivity. However, the precise mechanism by which NDV infection modulates DR expression and impacts TRAIL sensitivity in cancer cells remains unknown., Methods: Herein, we developed nonpathogenic NDV VG/GA strain-based recombinant NDV (rNDV) and TRAIL gene-containing rNDV (rNDV-TRAIL). We observed that viral infections lead to increased DR and TRAIL expressions and activate signaling proteins involved in intrinsic and extrinsic apoptosis pathways. Experiments were conducted in vitro using TRAIL-resistant CRC cells (HT-29) and nonresistant CRC cells (HCT116) and in vivo using relevant mouse models., Results: rNDV-TRAIL was found to exhibit better apoptotic efficacy than rNDV in CRC cells. Notably, rNDV-TRAIL had the stronger cancer cell-killing effect in TRAIL-resistant CRC cells. Western blot analyses showed that both rNDV and rNDV-TRAIL infections activate signaling proteins involved in the intrinsic and extrinsic apoptotic pathways. Notably, rNDV-TRAIL promotes concurrent intrinsic and extrinsic signal transduction in both HCT-116 and HT-29 cells., Conclusions: Therefore, rNDV-TRAIL infection effectively enhances DR expression in DR-depressed HT-29 cells. Moreover, the TRAIL protein expressed by rNDV-TRAIL effectively interacts with DR, leading to enhanced apoptosis in TRAIL-resistant HT-29 cells. Therefore, rNDV-TRAIL has potential as a promising therapeutic approach for treating TRAIL-resistant cancers., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Human voice recognition via skin-attachable devices has significant potential for gathering important physiological information from acoustic data without background noise interference. In this study, a highly sensitive and conductive wearable crack-based strain sensor was developed for voice-recognition systems. The sensor was fabricated using a double-layer structure of Ag nanoparticles (NPs) and Ag metal on a biocompatible polydimethylsiloxane substrate. The top metal layer acts as a conducting active layer, whereas the bottom Ag NP layer induces channel cracks in the upper layer, effectively hindering current flow. Subsequently, the double-layer film exhibits a low electrical resistance value (<5 × 10 -5 Ω cm), ultrahigh sensitivity (gauge factor = 1870), and a fast response/recovery time (252/168 μs). A sound wave was detected at a high frequency of 15 kHz with a signal-to-noise ratio (SNR) over 40 dB. The sensor exhibited excellent anti-interference characteristics and effectively differentiated between different voice qualities (modal, pressed, and breathy), with a systematic analysis revealing successful detection of the laryngeal state and glottal source. This ultrasensitive wearable sensor has potential applications in various physiological signal measurement methods, personalized healthcare systems, and ubiquitous computing.

Standard- and large-sized eggs of Trichuris trichiura were found in the feces of schoolchildren in Yangon, Myanmar during epidemiological surveys and mass deworming with albendazole in 2017-2019. The standard-sized eggs were identified as those of T. trichiura, but it was necessary to exclude the possibility of the large-sized eggs belonging to Trichuris vulpis, a dog whipworm. We conducted morphological and molecular studies to determine the species of the 2 types of Trichuris eggs. Individual eggs of both sizes were isolated from Kato-Katz fecal smears (n=20) and mechanically destroyed using a 23G injection needle. Nuclear DNA was extracted, and the 18S rRNA region was sequenced in 15 standard-sized eggs and 15 large-sized eggs. The average size of standard-sized eggs (T. trichiura) was 55.2×26.1 μm (range: 51.7-57.6×21.3-28.0 μm; n=97), whereas the size of large-sized eggs was 69.3×32.0 μm (range: 65.1-76.4×30.1-34.5 μm; n=20), slightly smaller than the known size of T. vulpis. Regarding standard-sized eggs, the 18S rRNA nucleotide sequences exhibited 100% homology with T. trichiura deposited in GenBank and 88.6-90.5% homology with T. vulpis. Regarding large-sized eggs, the nucleotide sequences showed 99.8-100% homology with T. trichiura in GenBank and 89.6-90.7% homology with T. vulpis. Both standard- and large-sized eggs of Trichuris spp. found in Myanmar schoolchildren during 2017-2019 were morphologically and molecularly confirmed to belong to T. trichiura. The conversion of eggs from smaller to large sizes might be due to anthelmintic treatments with albendazole.

LCN2/neutrophil gelatinase-associated lipocalin/24p3 (lipocalin 2) is a secretory protein that acts as a mammalian bacteriostatic molecule. Under neuroinflammatory stress conditions, LCN2 is produced and secreted by activated microglia and reactive astrocytes, resulting in neuronal apoptosis. However, it remains largely unknown whether inflammatory stress and neuronal loss can be minimized by modulating LCN2 production and secretion. Here, we first demonstrated that LCN2 was secreted from reactive astrocytes, which were stimulated by treatment with lipopolysaccharide (LPS) as an inflammatory stressor. Notably, we found two effective conditions that led to the reduction of induced LCN2 levels in reactive astrocytes: proteasome inhibition and macroautophagic/autophagic flux activation. Mechanistically, proteasome inhibition suppresses NFKB/NF-κB activation through NFKBIA/IκBα stabilization in primary astrocytes, even under inflammatory stress conditions, resulting in the downregulation of Lcn2 expression. In contrast, autophagic flux activation via MTOR inhibition reduced the intracellular levels of LCN2 through its pre-secretory degradation. In addition, we demonstrated that the N-terminal signal peptide of LCN2 is critical for its secretion and degradation, suggesting that these two pathways may be mechanistically coupled. Finally, we observed that LPS-induced and secreted LCN2 levels were reduced in the astrocyte-cultured medium under the above-mentioned conditions, resulting in increased neuronal viability, even under inflammatory stress. Abbreviations: ACM, astrocyte-conditioned medium; ALP, autophagy-lysosome pathway; BAF, bafilomycin A 1 ; BTZ, bortezomib; CHX, cycloheximide; CNS, central nervous system; ER, endoplasmic reticulum; GFAP, glial fibrillary acidic protein; GFP, green fluorescent protein; JAK, Janus kinase; KD, knockdown; LCN2, lipocalin 2; LPS, lipopolysaccharide; MACS, magnetic-activated cell sorting; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MTOR, mechanistic target of rapamycin kinase; NFKB/NF-κB, nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105; NFKBIA/IκBα, nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha; OVEX, overexpression; SLC22A17, solute carrier family 22 member 17; SP, signal peptide; SQSTM1, sequestosome 1; STAT3, signal transducer and activator of transcription 3; TNF/TNF-α, tumor necrosis factor; TUBA, tubulin, alpha; TUBB3/β3-TUB, tubulin, beta 3 class III; UB, ubiquitin; UPS, ubiquitin-proteasome system.

Opisthorchis viverrini infection is an emerging disease in Cambodia, especially in central and southeastern areas. However, its status in northern areas bordering Lao PDR has been relatively unknown. The present study was performed to investigate the status of O. viverrini infection among people in Preah Vihear and Stung Treng provinces through fecal examination to detect eggs and recovery of adult flukes from some of the egg-positive cases. Fecal examinations were performed on a total of 1101 people from 10 villages in the 2 provinces using the Kato-Katz thick smear technique. For recovery of adult flukes and other helminth parasites 10 volunteers positive for eggs of Opisthorchis viverrini and/or minute intestinal flukes (Ov/MIF), in Kampong Sangkae village, Preah Vihear province, were administered a single oral dose of 40 mg/kg praziquantel plus 5-10 mg/kg of pyrantel pamoate and purged with 40-50 g magnesium salts. Adult trematodes, together with nematodes and cestodes expelled in diarrheic stools were collected under a stereomicroscope or with the naked eye. The proportion of egg-positive cases for overall liver and intestinal helminths was high but not notably different between the 2 provinces, 65.5% in Preah Vihear versus 64.7% in Stung Treng. The average proportion of Ov/MIF egg-positive cases was 59.8%. A total of 315 adult specimens of O. viverrini were recovered from the 10 volunteers (4-98 specimens per individual; mean, 32). A smaller number of Haplorchis taichui adults, an intestinal fluke, were found mixed-infected in 7 (103 specimens in total; 1-31 per individual; mean, 15) of the 10 volunteers. Adult specimens of hookworms, Enterobius vermicularis, Trichostrongylus sp., and a Taenia tapeworm strobila were recovered in some cases. Based on the results, it has been confirmed that the surveyed areas in Preah Vihear and Stung Treng provinces, Cambodia, are highly endemic areas of O. viverrini infection with a low-grade mixed infection with H. taichui., (© 2023. The Author(s).)

Amorphous metal oxide semiconductor phototransistors (MOTPs) integrated with colloidal quantum dots (QDs) (QD-MOTPs) are promising infrared photodetectors owing to their high photoconductive gain, low off-current level, and high compatibility with pixel circuits. However, to date, the poor mobility of conventional MOTPs, such as indium gallium zinc oxide (IGZO), and the toxicity of lead (Pb)-based QDs, such as lead sulfide and lead selenide, has limited the commercial applications of QD-MOTPs. Herein, an ultrasensitive QD-MOTP fabricated by integrating a high-mobility zinc oxynitride (ZnON)-based MOTP and lead-free indium arsenide (InAs) QDs is demonstrated. A new gradated bandgap structure is introduced in the InAs QD layer that absorbs infrared light, which prevents carriers from moving backward and effectively reduces electron-hole recombination. Chemical, optical, and structural analyses confirm the movement of the photoexcited carriers in the graded band structure. The novel QD-MOTP exhibits an outstanding performance with a responsivity of 1.15 × 10 5 A W -1 and detectivity of 5.32 × 10 16 Jones at a light power density of 2 µW cm -2 under illumination at 905 nm., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

In this study, a temperature-insensitive strain sensor that detects only the strain without responding to the temperature was designed. The transport mechanism and associated temperature coefficient of resistance (TCR) of a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) thin film were modified through secondary doping with dimethyl sulfoxide (DMSO). Upon DMSO-doping, the carrier transport mechanism of the PEDOT:PSS thin film transitioned from hopping to band-like transport, with a morphological change. At the DMSO doping level, which caused the critical point of the transport transition, the resistance of the thin film was maintained with a change in temperature. Consequently, the TCR of the optimized PEDOT:PSS thin film was less than 9 × 10 -5 K -1 , which is 10 2 times lower than that of the as-prepared films. The carrier mobility of the PEDOT:PSS thin film was effectively improved with the morphological change due to DMSO doping and was investigated through combinational analysis. Ultimately, the wearable strain sensor prepared using the optimized PEDOT:PSS thin film responded stably to the applied strain with a gauge factor of 2 and exhibited excellent temperature anti-interference.

This study aims to confirm the effectiveness and safety of a prabotulinumtoxin type A (praBTX-A) injection in patients with bruxism and masseter hypertrophy. The study included patients who ground or clenched their teeth while sleeping and had computed tomography (CT) scans that showed a maximum thickness of the masseter muscle of 15 mm or more. The praBTX-A was administered bilaterally into the masseter muscles; 15 U/side for group 1, 25 U/side for group 2, and 35 U/side for group 3. CT scans and bruxism questionnaires were conducted before and eight weeks after the injection. Thirty-seven patients were enrolled, but three dropped out due to loss of follow-up. After injection, masseter thickness decreased to 15.1 ± 2.0 mm for group 1, 14.3 ± 2.9 mm for group 2, and 13.4 ± 1.8 mm for group 3 (p = 0.043). Group 3 showed a statistically significant lower masseter thickness compared to group 1 (p = 0.039). Both subjective and objective frequencies of bruxism decreased for all groups, but there were no significant differences in either subjective (p = 0.396) or objective frequencies (p = 0.87) between the groups after the injection. The results of this study suggest that praBTX-A injection is a safe and effective treatment for bruxism and masseter hypertrophy. A dosage of 35 IU/side can effectively decrease masseter thickness and relieve bruxism symptoms. Even the minimum dosage of 15 IU/side can contribute to improvements in bruxism symptoms. This investigation provides valuable information for managing bruxism that is associated with hypertrophic masseter muscles., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The attitude toward telerehabilitation (TR) among therapists (191 physical therapists and 159 occupational therapists) in Korea was surveyed. The survey consisted of 15 questions in the following 8 domains: awareness(AW), attitude (AT), perceived usefulness (PU), perceived behavioral control (PBC), self-efficacy (SE), facilitating conditions (FC), barriers (B), and behavioral intention (BI). Therapists with experience in TR responded with higher scores in all domains except B, regardless of their specialty. The most perceived barriers to TR were unmatched insurance fees and a lack of technical support. Experience with TR was a major factor in attitude and behavior intention toward TR., Competing Interests: Conflict of Interest: The authors have no potential conflicts of interest to disclose., (Copyright © 2023. Korean Society for Neurorehabilitation.)

Head louse infestation is a significant public health problem across the world, particularly among preschool and primary schoolchildren. This study investigated the trends of head louse infestation in the Republic of Korea over a 9-year period (2011-2019), targeting primary schoolchildren in 3 areas of Seoul, 4 other large cities, and 9 provinces. A survey was administered annually by the health staff of each regional office (n= 16) of the Korea Association of Health Promotion (KAHP). The branch offices of KAHP examined a total of 51,508 primary schoolchildren, comprising 26,532 boys and 24,976 girls. Over the 9-year survey, a total of 1,107 (2.1%) schoolchildren tested positive for adults and/or nits of Pediculus humanus capitis. The prevalence was 2.8% (133/4,727) in 2011-2012 and gradually decreased to 0.8% (49/6,461) in 2019 (P< 0.05). Head lice were found more frequently in girls (3.0%; 746/24,976) than in boys (1.4%; 361/26,532) (P< 0.05). In terms of geographic localities, the highest infestation rate, 4.7% (average prevalence over 9 years), was observed in southern Seoul (Gangnam branch of KAHP), whereas the lowest infestation rate, 0.7%, was seen in Gyeongsang (north and south provinces) and western Seoul. Although the prevalence decreased significantly during the 9-year period, head louse infestation remains a health and hygiene issue among primary schoolchildren in the Republic of Korea. Regular surveys along with health education are needed to further improve children's hair hygiene.

One of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far failed to significantly improve outcomes. Baicalin, or 5,6,7-trihydroxyflavone, is a type of flavonoid which has been shown to possess a variety of biological characteristics, including antioxidative and anti-inflammatory effects and protection of I/R injury. In vitro wound scratch assay was first used to assess the function of baicalin in wound healing. We established a mouse model of advanced stage pressure ulcers with repeated cycles of I/R pressure load. In this model, topically applied baicalin (100 mg/mL) induced a significant increase in the wound healing process measured by wound area. Histological examination of the pressure ulcer mouse model showed faster granulation tissue formation and re-epithelization in the baicalin-treated group. Next, baicalin downregulated pro-inflammatory cytokines (IL-6 and IL-1β), while upregulating the anti-inflammatory IL-10. Additionally, baicalin induced an increase in several growth factors (VEGF, FGF-2, PDGF-β, and CTGF), promoting the wound healing process. Our results suggest that baicalin could serve as a promising agent for the treatment of pressures ulcers.

Even though chemotherapy regimens for treating cancer by inducing apoptosis are extensively utilized, their therapeutic effect is hindered by multiple limitations. Thus, a combination of other types of anticancer modalities is urgently needed. Herein, a tannic acid (TA)-Fe 3+ -coated doxorubicin (DOX)-encapsulated 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(poly(ethylene glycol))-2000] (ammonium salt) (DSPE-PEG) micelle (TFDD) for apoptosis/ferroptosis-mediated immunogenic cell death (ICD) is reported. By coating TA-Fe 3+ on the surface of DOX-loaded micelles, an apoptotic agent and a ferroptotic agent are simultaneously delivered into the cancer cells and induce cell death. Furthermore, the intracellular oxidative environment generated by the apoptosis/ferroptosis hybrid pathway stimulates the endoplasmic reticulum (ER) and leads to ICD induction. The in vivo results show that the combination treatment of TFDD and anti-programmed death-ligand 1 antibodies (anti-PD-L1) considerably inhibits tumor growth and improves antitumor immunity by activating CD4 + and CD8 + T cells and decreasing the ratio of regulatory T cells (Treg) to CD4 + T cells. This study suggests that the apoptosis/ferroptosis-mediated ICD inducer may offer a potent strategy for enhanced cancer immunotherapy.

A survey of intestinal helminths targeting 1,440 schoolchildren in 12 primary schools on Kome Island (Lake Victoria), Tanzania, revealed small trematode eggs in 19 children (1.3%), seemingly of a species of Haplorchis or Heterophyes. The eggs were molecularly confirmed to be Haplorchis pumilio on the basis of 18S and 28S rDNA sequences.

The integration of quantum dots (QDs) into device arrays for high-resolution display and imaging sensor systems remains a significant challenge in research and industry because of issues associated with the QD patterning process. It is difficult for conventional patterning processes such as stamping, inkjet printing, and photolithography to employ QDs and fabricate high-resolution patterns without degrading the properties of QDs. Here, we introduce a novel strategy for the QD patterning process by treating QDs with a bifunctional ligand for acid-base reaction-assisted photolithography. Bifunctional ligands, such as MPA (mercaptopropionic acid) or TGA (thioglycolic acid), have a carboxyl group on one side that allows the QDs to be etched along with the photoresist (PR) by the base developer, while on the opposite side the ligands have a thiol group that passivates the QD surface. Passivating MPA ligands on QDs facilitates patterning of QD films and makes them compatible with harsh photolithography processes. We successfully achieved the patterning of QDs down to 5 μm. We also fabricated high-resolution patterned QD light-emitting diodes (LEDs) and QD photodetector arrays. Our patterning process provides precise control for the fabrication of highly integrated QD-based optoelectronic devices.

Background: The coronavirus Disease 2019 (COVID-19) is a respiratory disease that has caused extensive ravages worldwide since being declared a pandemic by the World Health Organization (WHO). Unlike initially predicted by WHO, the incidence and severity of COVID-19 appeared milder in many Low-to-Middle-Income Countries (LMIC). To explain this noticeable disparity between countries, many hypotheses, including socio-demographic and geographic factors, have been put forward. This study aimed to estimate the possible association of parasitic diseases with COVID-19 as either protective agents or potential risk factors., Methods/principal Findings: A country-level ecological study using publicly available data of countries was conducted. We conceptualized the true number of COVID-19 infections based on a function of test positivity rate (TPR) and employed linear regression analysis to assess the association between the outcome and parasitic diseases. We considered demographic, socioeconomic, and geographic confounders previously suggested. A notable heterogeneity was observed across WHO regions. The countries in Africa (AFRO) showed the lowest rates of COVID-19 incidence, and the countries in the Americas (AMRO) presented the highest. The multivariable model results were computed using 165 countries, excluding missing values. In the models analyzed, lower COVID-19 incidence rates were consistently observed in malaria-endemic countries, even accounting for potential confounding variables, Gross Domestic Product (GDP) per capita, the population aged 65 and above, and differences in the duration of COVID-19. However, the other parasitic diseases were not significantly associated with the spread of the pandemic., Conclusions/significance: This study suggests that malaria prevalence is an essential factor that explains variability in the observed incidence of COVID-19 cases at the national level. Potential associations of COVID-19 with schistosomiasis and soil-transmitted helminthiases (STHs) are worthy of further investigation but appeared unlikely, based on this analysis, to be critical factors of the variability in COVID-19 epidemic trends. The quality of publicly accessible data and its ecological design constrained our research, with fundamental disparities in monitoring and testing capabilities between countries. Research at the subnational or individual level should be conducted to explore hypotheses further., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study is aimed at investigating the pattern of change occurring in respiratory pathogens before and after the outbreak of COVID-19, a type of viral pneumonia for which a pandemic was declared (March 2020). The results were analyzed by gender and age to identify the association between personal hygiene and prevention of infection by respiratory pathogens., Methods: A retrospective analysis was performed on 39,814 sputum, bronchial aspirate, and transtracheal aspirate samples obtained from 15,398 patients visiting a university hospital, located in Chungcheongnam-do, South Korea, between January 2018 and December 2021. From 4,454 patients whose samples were culture positive for bacteria, 6,389 strains were isolated and further cultured., Results: The mean age of the outpatients with respiratory pathogens was 66.2 years, and the comparison of the culture test results by gender showed that 64.9% (2,892/4,454) were male and 35.1% (1,562/4,454) were female. Compared to the pre-COVID-19 pandemic period, the number of outpatients with a request for respiratory microbial cultures after the onset of the pandemic was reduced by 20.7% and the number of outpatients with a positive culture result was reduced by 23.0%. The number of respiratory samples received was reduced by 6.7% after the pandemic, while the sample positive rate was reduced by 18.3%. Among the isolated microbial strains, there was a significant decrease of 43.1% for the Acinetobacter baumannii complex, 60.5% for Streptococcus pneumoniae , 67.2% for Haemophilus influenzae , and 78.1% for Moraxella catarrhalis when compared with pre-COVID-19 levels. The distribution of respiratory microbial strains by age group showed that the highest percentage of isolated strains was in patients in their 70s., Conclusions: The improvements in personal hygiene due to the COVID-19 pandemic exerted a substantial influence on the pattern of change in other common respiratory microorganisms, which highlights the importance of personal hygiene management in the prevention of respiratory infections., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Ki Yeon Kim et al.)

Fascioliasis, a food-borne helminthiasis, is primarily a disease of cattle and sheep that occasionally occurs in humans. The aquatic perennial herb water dropwort ( Oenanthe javanica ) has been identified as the primary source of human infections in Korea. Recently, a cluster of patients who had not ingested water dropwort, but had the use of a green vegetable delivery service in common was diagnosed with fascioliasis. Our study aimed to identify the association between the green vegetable juice delivery service and the occurrence of human fascioliasis. Patients with liver abscesses and eosinophilia were enrolled in this study. They were categorized into fascioliasis or non-fascioliasis groups according to serological test results, clinical manifestations, and computed tomography or magnetic resonance imaging findings. Patients were classified into the fascioliasis group when ova or the adult worms of the Fasciola species were detected or serological tests were positive, with compatible clinical and radiological findings. We included 30 patients in this study; 15 were assigned to the fascioliasis group and the remaining 15 to the non-fascioliasis group. The proportion of patients who utilized the juice delivery service was significantly higher in the fascioliasis group than in the non-fascioliasis group (53.3% vs. 0%, P  < 0.01). Most of the other patients in the fascioliasis group had known risk factors and the intake of water dropwort or other raw vegetables. This study suggests that human fascioliasis could be transmitted by green vegetable juice produced and delivered by modern industrial systems. Further research on the product, industry and farm-level situations is required to validate these findings., Competing Interests: We have no conflicts of interest related to this work., (© 2022 Published by Elsevier B.V.)

Toxoplasma gondii is an intracellular protozoan parasite that can modulate the microenvironment of infected hosts and is known to be associated with the incidence of brain tumor growth. In this study, we suggested that the exosomal microRNA-21 derived from Toxoplasma infection would contribute to the growth of brain tumors. Exosomes of BV2 microglial cells infected with Toxoplasma were characterized and confirmed internalization to U87 glioma cells. Exosomal miRNA expression profiles were analyzed using microRNA array and miR-21A-5p associated with Toxoplasma and tumor sorted. We also examined the mRNA level of tumor-associated genes in U87 glioma cells by changing the level of miR-21 within exosomes and the effects of exosomes on the proliferation of human U87 glioma cells. Expression of miRNA-21 was increased and anti-tumorigenic genes (FoxO1, PTEN, and PDCD4) were decreased in exosomes within T. gondii-infected U87 glioma cells. Toxoplasma-infected BV2-derived exosomes induced proliferation of U87 glioma cells. The exosomes induced the growth of U87 cells in a mouse tumor model. We suggest that the increased exosomal miR-21 from Toxoplasma-infected BV2 microglial cells may play an important role as a cell growth promotor of U87 glioma cells through a down-regulation of anti-tumorigenic genes., (© 2022. The Author(s).)

Foodborne trematodes (FBT) of public health significance include liver flukes ( Clonorchis sinensis, Opisthorchis viverrini, O. felineus, Fasciola hepatica and F. gigantica ), lung flukes ( Paragonimus westermani and several other Paragonimus spp.) and intestinal flukes, which include heterophyids ( Metagonimus yokogawai, Heterophyes nocens and Haplorchis taichui ), echinostomes ( Echinostoma revolutum, Isthmiophora hortensis, Echinochasmus japonicus and Artyfechinostomum malayanum ) and miscellaneous species, including Fasciolopsis buski and Gymnophalloides seoi . These trematode infections are distributed worldwide but occur most commonly in Asia. The global burden of FBT diseases has been estimated at about 80 million, however, this seems to be a considerable underestimate. Their life cycle involves a molluscan first intermediate host, and a second intermediate host, including freshwater fish, crustaceans, aquatic vegetables and freshwater or brackish water gastropods and bivalves. The mode of human infection is the consumption of the second intermediate host under raw or improperly cooked conditions. The major pathogenesis of C. sinensis and Opisthorchis spp. infection includes inflammation of the bile duct which leads to cholangitis and cholecystitis, and in a substantial number of patients, serious complications, such as liver cirrhosis and cholangiocarcinoma, may develop. In lung fluke infections, cough, bloody sputum and bronchiectasis are the most common clinical manifestations. However, lung flukes often migrate to extrapulmonary sites, including the brain, spinal cord, skin, subcutaneous tissues and abdominal organs. Intestinal flukes can induce inflammation in the intestinal mucosa, and they may at times undergo extraintestinal migration, in particular, in immunocompromised patients. In order to control FBT infections, eating foods after proper cooking is strongly recommended.

Stretchable electrodes are widely used in next-generation wearable electronics. Recent studies incorporated designs that help rigid electrodes attain stretchability. However, these structures exhibited unsatisfactory charge/signal extraction efficiency because of their low areal fill factor. Additionally, they cannot be photolithographically patterned on polymer substrates because of their low adhesion, requiring additional complicated fabrication steps. We developed photolithographically patternable stretchable electrodes with complete coverage and enhanced charge-extraction efficiency. The electrodes, comprising double layers, included a chemically treated Ag nanowire mesh and Au thin film. The interfacial linker role of polyvinylpyrrolidone chemically strengthened the interfacial bonds, and the reinforced concrete structure of nanowire-embedded metal thin films enhanced the mechanical properties. Therefore, the electrodes provided superior efficiency and stability in capturing physical, electromagnetic, and electrophysiological signals while exceeding the existing stretchable electrode limits. A broad range of applications are foreseen, such as electrocardiogram sensing electrodes, strain sensors, temperature sensors, and antennas.

Wound healing is a complicated cascading process; disequilibrium among reparative processes leads to the formation of pathologic scars. Herein, we explored the role of mortalin in scar formation and its association with the interleukin-1α receptor using in vitro and in vivo models. To investigate the effects of mortalin, we performed an MTT cell viability assay, qRT-PCR, and Western blot analyses, in addition to immunofluorescence and immunoprecipitation studies using cultured fibroblasts. A rat incisional wound model was used to evaluate the effect of a mortalin-specific shRNA (dE1-RGD/GFP/shMot) Ad vector in scar tissue. In vitro, the mortalin-treated human dermal fibroblast displayed a significant increase in proliferation of type I collagen, α-smooth muscle actin, transforming growth factor-β, phospho-Smad2/3-complex, and NF-κB levels. Immunofluorescence staining revealed markedly increased mortalin and interleukin-1α receptor protein in keloid tissue compared to those in normal tissue, suggesting that the association between mortalin and IL-1α receptor was responsible for the fibrogenic effect. In vivo, mortalin-specific shRNA-expressing Ad vectors significantly decreased the scar size and type-I-collagen, α-SMA, and phospho-Smad2/3-complex expression in rat incisional scar tissue. Thus, dE1-RGD/GEP/shMot can inhibit the TGF-β/α-SMA axis and NF-κB signal pathways in scar formation, and blocking endogenous mortalin could be a potential therapeutic target for keloids.

Background: The prompt detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important in the therapeutic management of infected patients. Rapid diagnostic tests are widely used for this purpose. This study aimed to evaluate the clinical performance of four SARS-CoV-2 immunoglobulin IgG/IgM rapid diagnostic tests in the detection of SARS-CoV-2., Methods: Nasopharyngeal and oropharyngeal swabs and/or sputum were collected from 30 patients infected with SARS-CoV-2 and 30 healthy volunteers. All specimens were tested using four SARS-CoV-2 IgG/IgM rapid diagnostic tests and real-time polymerase chain reaction. We assessed the clinical sensitivity and specificity of the tests., Results: The clinical sensitivity of FREND™, SsmarTest™, BIOCREDIT™, and IVDLAB™ was 96.67%, 100.00%, 100.00%, and 96.67%, respectively, compared to real-time polymerase chain reaction. The clinical specificity was 96.67%, 100.00%, 86.67%, and 96.67%, respectively., Conclusion: These findings could expedite the detection of SARS-CoV-2 and thus reduce the risk of further transmission of the virus., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Cancer is a multifactorial and deadly disease. Despite major advancements in cancer therapy in the last two decades, cancer incidence is on the rise and disease prognosis still remains poor. Furthermore, molecular mechanisms of cancer invasiveness, metastasis, and drug resistance remain largely elusive. Targeted cancer therapy involving the silencing of specific cancer-enriched proteins by small interfering RNA (siRNA) offers a powerful tool. However, its application in clinic is limited by the short half-life of siRNA and warrants the development of efficient and stable siRNA delivery systems. Oncolytic adenovirus-mediated therapy offers an attractive alternative to the chemical drugs that often suffer from innate and acquired drug resistance. In continuation to our reports on the development of oncolytic adenovirus-mediated delivery of shRNA, we report here the replication-incompetent (dAd/shErbB3) and replication-competent (oAd/shErbB3) oncolytic adenovirus systems that caused efficient and persistent targeting of ErbB3. We demonstrate that the E1A coded by oAd/shErbB, in contrast to dAd/shErbB, caused downregulation of ErbB2 and ErbB3, yielding stronger downregulation of the ErbB3-oncogenic signaling axis in in vitro models of lung and breast cancer. These results were validated by in vivo antitumor efficacy of dAd/shErbB3 and oAd/shErbB3.

Background: While immune checkpoint inhibitors are becoming a standard of care for multiple types of cancer, the majority of patients do not respond to this form of immunotherapy. New approaches are required to overcome resistance to immunotherapies., Methods: We investigated the effects of adenoviral p53 (Ad-p53) gene therapy in combination with immune checkpoint inhibitors and selective IL2 or IL15 CD122/132 agonists in the aggressive B16F10 tumor model resistant to immunotherapies. To assess potential mechanisms of action, pre- and post- Ad-p53 treatment biopsies were evaluated for changes in gene-expression profiles by Nanostring IO 360 assays., Results: The substantial synergy of "triplet" Ad-p53 + CD122/132 + anti-PD-1 therapy resulted in potential curative effects associated with the complete tumor remissions of both the primary and contralateral tumors. Interestingly, contralateral tumors, which were not injected with Ad-p53 showed robust abscopal effects resulting in statistically significant decreases in tumor size and increased survival (p < 0.001). None of the monotherapies or doublet treatments induced the complete tumor regressions. Ad-p53 treatment increased interferon, CD8 + T cell, immuno-proteosome antigen presentation, and tumor inflammation gene signatures. Ad-p53 treatment also decreased immune-suppressive TGF-beta, beta-catenin, macrophage, and endothelium gene signatures, which may contribute to enhanced immune checkpoint inhibitor (CPI) efficacy. Unexpectedly, a number of previously unidentified, strongly p53 downregulated genes associated with stromal pathways and IL10 expression identified novel anticancer therapeutic applications., Conclusions: These results imply the ability of Ad-p53 to induce efficacious local and systemic antitumor immune responses with the potential to reverse resistance to immune checkpoint inhibitor therapy when combined with CD122/132 agonists and immune checkpoint blockade. Our findings further imply that Ad-p53 has multiple complementary immune mechanisms of action, which support future clinical evaluation of triplet Ad-p53, CD122/132 agonist, and immune checkpoint inhibitor combination treatment., (© 2021. The Author(s).)

Human Pseudoterranova decipiens larval infections were diagnosed by molecular analysis of mitochondrial cox1 and nd1 genes in 12 health check-up patients in South Korea during 2002-2020. Based on high genetic identity (99.3%-100% for cox1 and 96.7%-98.0% for nd1), we identified all 12 larvae as P. decipiens sensu stricto.

The Korea Atomic Energy Research Institute has recently proposed and developed a novel cesium-free negative hydrogen/deuterium ion source system based on two pulsed plasma sources for fusion and particle accelerator applications. The main feature of this ion source system is the use of both magnetic filters and plasma pulsing (also called the temporal filter). The system operates with two alternate pulsing sequences related to the respective plasma sources, thereby switching the plasmas in the after-glow state in an alternating manner. This study investigates the temporal behavior of deuterium negative ions in the system in a qualitative way by conducting a time-resolved measurement of laser photodetachment current commensurate with the negative ion density. In preliminary experiments, the current in the initial after-glow state remains higher than in the active-glow state identical to a steady-state continuous wave plasma, and the ratio reaches a maximum of about three times. This indicates that the pulsing gives highly efficient negative ion volume formation. Furthermore, it is observed that the time duration when the current is maintained at high values can be prolonged (or modulated) with the alternate dual pulsing, which is not possible with conventional single pulsing. These results provide a clue that the multi-pulsed ion source system may offer a continuous supply of negative ions at high densities and consequently become an alternative to cesium seeded ion sources.

Since the SARS-CoV-2 infection was identified in December 2019, SARS-CoV-2 infection has rapidly spread worldwide and has become a significant pandemic disease. In addition, human death and serious health problem caused by SARS-CoV-2 infection, the socio-economic impact has been very serious. Here, we describe the development of the viral vector vaccine, which is the receptor-binding domain (RBD) of SARS-CoV-2 expressed on the surface of Newcastle disease virus (LVP-K1-RBD19). The RBD protein concentrations on the viral surface were measured by the sandwich ELISA method. 106.7 TCID50/ml of LVP-K1-RBD19 has a 0.17 μg of RBD protein. Optical density (OD) values of mouse sera inoculated with 10 μg of RBD protein expressed on the surface of LVP-K1-RBD19 generated 1.78-fold higher RBD-specific antibody titers than mice inoculated with 10 μg RBD protein with alum at 28 dpi. Moreover, mice inoculated with 10 μg of RBD protein expressed on the surface of LVP-K1-RBD19 virus showed more than 80% neutralization at 1:256 against the SARS-CoV-2 pseudovirus. These results demonstrated that inactivated LVP-K1-RBD19 virus produces neutralizing antibodies against SARS-CoV-2 in a short period and could be elect protective immunity in humans and LVP-K1-RBD19 will be a good candidate for the COVID-19 vaccine., Competing Interests: The authors have declared that no competing interests exist.

Objectives: C-reactive protein is well known as an inflammatory indicator in injury, infection, and cancer. However, little is known about its role in poisoning. C-reactive protein levels first increase and then decrease within several days during poisoning management. This study aimed to verify the C-reactive protein change pattern and its clinical co-infection possibility in patients with poisoning., Methods: Daily C-reactive protein levels of the patients with poisoning, who were admitted for more than 5 days, were measured. Microbial cultures were conducted, and fever (⩾38°C) and infection-related symptoms were investigated., Results: In the enrolled 56 patients, the initial median C-reactive protein levels at hospital day 1, 2, 3, 4, and 5 were 0.28, 4.85, 10.91, 10.57, and 6.68 mg/dL, respectively. C-reactive protein level was the highest at hospital day 3 and decreased thereafter. No statistical difference was observed in the daily and maximal C-reactive protein levels between the culture-positive and culture-negative groups. The levels at hospital days 3-5 and the maximal level were 8.4, 9.2, 5.49, and 11.02 mg/dL, respectively, in non-fever group. The levels at hospital days 3-5 and the maximal level were 7.4, 9.2, 4.74, and 10.81 mg/dL, respectively, in non-symptoms group. Levels at hospital days 3-5 and the maximal level were 5.21, 4.93, 3.7, and 5.28 mg/dL, respectively, in all-negative (culture-negative without fever or infection symptoms) group., Conclusions: Acute rise and fall of C-reactive protein levels can be observed in the infection-unlikely patients with poisoning. The levels were similar to bacterial infection levels, possibly due to the drug reaction itself, rather than for superimposed infections., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Glioblastoma is one of the most serious brain cancer. Previous studies have demonstrated that PTEN function disorder affects the causing and exacerbation of glioblastoma. Newcastle disease virus (NDV) has been studied as a cancer virotherapeutics. In this study, PTEN gene was delivered to glioblastoma by recombinant NDV (rNDV) and translated into protein at the cytoplasm of the glioblastoma., Methods: We did comparison tests PTEN protein expression efficiency and oncolytic effect depend on the PTEN gene insertion site at the between NP and P genes and the between P and M gene. PTEN protein mRNA transcription, translation in glioblastoma cell, and functional PTEN protein effect of the rNDV in vitro and in vivo test performed using western blotting, RT-qPCR, MTT assay, and Glioblastoma xenograft animal model test., Results: The result of this study demonstrates that rNDV-PTEN kills glioblastoma cells and reduces cancer tissue better than rNDV without the PTEN gene. In molecular immunological and cytological assays, PTEN expression level was high at located in the between NP and P gene, and PTEN gene was successfully delivered to the glioblastoma cell using rNDV and PTEN gene translated to functional protein and inhibits hTERT and AKT gene., Conclusions: PTEN gene enhances the oncolytic effect of the rNDV. And our study demonstrated that NP and P gene site is better than P and M gene site which is commonly and conventionally used. PTEN gene containing rNDV is a good candidate virotherapeutics for glioblastoma., (© 2022. The Author(s).)

The Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the family Coronaviridae and genus Betacoronavirus, has been recognized as a highly pathogenic virus. Due to the lack of therapeutic or preventive agents against MERS-CoV, developing an effective vaccine is essential for preventing a viral outbreak. To address this, we developed a recombinant S1 subunit of MERS-CoV spike protein fused with the human IgG4 Fc fragment (LV-MS1-Fc) in Chinese hamster ovary (CHO) cells. Thereafter, we identified the baculovirus gp64 signal peptide-directed secretion of LV-MS1-Fc protein in the extracellular fluid. To demonstrate the immunogenicity of the recombinant LV-MS1-Fc proteins, BALB/c mice were inoculated with 2.5 μg of LV-MS1-Fc. The inoculated mice demonstrated a significant humoral immune response, measured via total IgG and neutralizing antibodies. In addition, human dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with LV-MS1-Fc showed the protective capacity of LV-MS1-Fc against MERS-CoV with no inflammatory cell infiltration. These data showed that the S1 and Fc fusion protein induced potent humoral immunity and antigen-specific neutralizing antibodies in mice, and conferred protection against coronavirus viral challenge, indicating that LV-MS1-Fc is an effective vaccine candidate against MERS-CoV infection., (Copyright © 2021. Published by Elsevier B.V.)